L-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro.
Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by which L-N-acetylcysteine (L-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous...
| Publicado en: | Acta Oto-Laryngologica Vol. 138; no. 8; pp. 676 - 685 |
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| Autores principales: | , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Taylor & Francis Ltd
Aug2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=130416808&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 130416808 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00016489 B6D jtl: Acta Oto-Laryngologica issn: 00016489 maglogo: Y pubinfo: dt: Aug2018 vid: 138 iid: 8 pid: 377 pub: Taylor & Francis Ltd place: Philadelphia, Pennsylvania artinfo: ui: 130416808 130416808 130416808 10.1080/00016489.2018.1440086 130416808 ppf: 676 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: L-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro. aug: au: Tillinger, Joshua A. Gupta, Chhavi Ila, Kadri Ahmed, Jamal Mittal, Jeenu Van De Water, Thomas R. Eshraghi, Adrien A. affil: Department of Otolaryngology, Hearing Research Laboratory, Miller School of Medicine University of Miami, Miami, FL, USA sug: subj: Acetylcysteine Pharmacodynamics Hair Cells Drug Effects Tumor Necrosis Factor Oxidative Stress Drug Effects Ototoxicity Animal Studies Rats In Vitro Studies Hearing Loss, Noise-Induced Prevention and Control Animals, Laboratory Ear Drug Effects Normal Saline Reactive Oxygen Species Lipid Peroxidation Mitochondria Physiology Cell Viability Staining and Labeling Glutathione Apoptosis Drug Effects ab: Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by which L-N-acetylcysteine (L-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. L-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined. Design: Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 μg/ml, N = 12); (3) TNFα+L-NAC (5 mM, N = 12); (4) TNFα+L-NAC (10 mM, N = 12); or (5) L-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed. Results: L-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+L-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+L-NAC (5 mM) treated explants (p < 0.001). Conclusions: L-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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